肠易激综合征早期生活事件模型下的大鼠结肠肠神经可塑性研究  

Neonatal maternal deprivation triggers long term alterations in enteric neuronal plasticity in rat colon

作　　者：赵敏[1] 郭友逢[1] 张萌[1] 李智[1] 

机构地区：[1]中山大学附属第一医院病理科,广东广州510080

出　　处：《解剖学研究》2013年第2期120-125,共6页Anatomy Research

摘　　要：目的从神经可塑性角度探讨肠易激综合征的可能发病机制、临床特征及治疗方法。方法雄性SD大鼠出生后连续13 d每天分离3 h。腹壁撤退反射实验用来检测内脏痛觉过敏。肠神经系统结构可塑性可以通过铺片技术和免疫荧光技术,比较近端结肠神经节(HuD阳性细胞)的大小和数目以及胶质细胞(GFAP)的变化来检测。检测近端结肠多组肌间神经丛和黏膜下神经丛肠神经递质类型(ChAT-、VIP-、nNOS-、calbindin-TrKA-、P75-阳性细胞),分析神经递质的可塑性变化。结果新生期应激可致成年鼠内脏敏感性增高,新生期母婴分离可以诱导肠神经结构改变,导致神经元肥大和增生、胶质细胞与神经元的比例增高。神经递质方面,新生期母婴分离组P75和TrkA表达(黏膜下神经丛、肌间神经丛)较正常组均明显增加。ChAT在肌间神经丛表达明显增加,VIP在黏膜下神经丛表达降低,nNOS在肌间神经丛表达增高,Cabindin表达未见明显异常。结论新生期母婴分离可以引起大鼠结肠肠神经可塑性的长期改变。新生期母婴分离诱导的内脏高敏感性中存在肠神经系统可塑性。早期生活事件是引起成年后肠神经系统可塑性改变的重要原因。Objective To discuss pathogenesis of irritable bowel syndrome from the perspectives of neuronal plasticity, clinical features and treatment, ntheods Male SD rat pups will be subjected to 180-min daily NMS or NH for 13 consecutive days. Abdominal withdrawal reflex （AWR） test will be used to detect visceral hyperalgesia. The ENS structural plasticity will be assessed through comparing the size and/or the number of ganglia （identified with HuD- immunoreactive neurons） and glial cells （identified with glial fibrillary acidic protein （GFAP）- immunoreactive） with that of control group of rats.The neurochemical plasticity will be analyzed through the immunohistochemical methods for CHAT, vasoactive intestinal peptide （VIP）, neuronal nitric oxide synthase （nNOS）, Calbindin, TrkA and P75 （low-affinity recetpor for NGF） in whole mounts of proximal colonic myenteric and submucosal plexus. Results NMS promotes visceral sensitivity to rectal distention. Maternal deprivation triggered structural changes in enteric ganglia, including neuronal hypertrophy and hyperplasia and increase of the ratio gila/neurons. For the neurochemical coding of enteric neurons, we showed a marked increase in the P75 and TrkA immunoreactive neurons of the submucosal plexus and myenteric plexus with an increase of ChAT immunoreactive neurons in the myenteric plexus and a decrease of VIP immunoreactive neurons in the submucosal plexus. Meanwhile, NMS still induced a significant increase in the nNOS immunoreactive neurons in the myenteric plexus. Cabindin immunoreactive neurons had no statistical significance. Conclusion NMS promotes long term alterations in enteric neuronal plasticity in rat colon. ENS plasticity exists in NMS-induced visceral hyperalgesia. Our results suggest a role for early life experience is in the regulation of ENS plasticity in later life.

关 键 词：肠易激综合征 肠神经系统 可塑性 新生期母婴分离 

分 类 号：R574.62[医药卫生—消化系统]